The objective of the proposed investigation is to study the biochemical parameters of the genetic neurological disorder, metachromatic leukodystrophy (MLD). The biochemical defect in MLD is a dysfunction of the lysosomal enzyme cerebroside sulfatase (also known as arylsulfatase A), which is essential for the normal metabolism of the myelin component, cerebroside sulfate. MLD is actually a group of disorders including the classical forms (late infantile, juvenile and adult), multiple sulfatase deficiency disorder, cerebroside sulfatase activator deficiency, and a number of atypical forms which are as yet uncharacterized. A benign deficiency, pseudo arylsulfatase A deficiency, is also known. The primary experimental model will be fibroblasts in culture derived from individuals with various forms of MLD. The present studies will focus on three aspects of MLD. (1) The fibroblast cerebroside sulfate loading system: the cerebroside sulfate uptake process and the intracellular cerebroside sulfatase reaction in normal fibroblasts will be characterized to allow examination of various MLD fibroblasts for specific anomalies (2) Fibroblasts arysulfatase A gene products: antibody isolation technique will be applied to define certain structural properties as well as to trace the natural history of arylsulfatase A in normal fibroblasts. This will serve as a reference to examine MLD fribroblasts for possible defects in these parameters. (3) Multiple sulfatase deficiency disorder in fibroblasts: since we now know that the arylsulfatase A gene is intact and the enzyme deficiency is the result of a defect in another system, probes to idenfity the primary defect will be conducted. The mechanism of its effect on arylsulfatase A as well as on other sulfatase will then be investigated.